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@ARTICLE{Hawwari:284080,
author = {Hawwari, Ibrahim and Rossnagel, Lukas and Rosero, Nathalia
and Maasewerd, Salie and Vasconcelos, Matilde B and
Jentzsch, Marius and Demczuk, Agnieszka and Teichmann, Lino
L and Meffert, Lisa and Bertheloot, Damien and Secchim
Ribeiro, Lucas and Kallabis, Sebastian and Meissner, Felix
and Arditi, Moshe and Atici, Asli E and Noval Rivas, Magali
and Franklin, Bernardo S},
title = {{P}latelet transcription factors license the
pro-inflammatory cytokine response of human monocytes},
journal = {EMBO molecular medicine},
volume = {16},
number = {8},
issn = {1757-4676},
address = {[London]},
publisher = {Nature Publishing Group UK},
reportid = {DZNE-2026-00088},
pages = {1901 - 1929},
year = {2024},
abstract = {In humans, blood Classical CD14+ monocytes contribute to
host defense by secreting large amounts of pro-inflammatory
cytokines. Their aberrant activity causes hyper-inflammation
and life-threatening cytokine storms, while dysfunctional
monocytes are associated with 'immunoparalysis', a state of
immune hypo responsiveness and reduced pro-inflammatory gene
expression, predisposing individuals to opportunistic
infections. Understanding how monocyte functions are
regulated is critical to prevent these harmful outcomes. We
reveal platelets' vital role in the pro-inflammatory
cytokine responses of human monocytes. Naturally low
platelet counts in patients with immune thrombocytopenia or
removal of platelets from healthy monocytes result in
monocyte immunoparalysis, marked by impaired cytokine
response to immune challenge and weakened host defense
transcriptional programs. Remarkably, supplementing
monocytes with fresh platelets reverses these conditions. We
discovered that platelets serve as reservoirs of key
cytokine transcription regulators, such as NF-κB and MAPK
p38, and pinpointed the enrichment of platelet NF-κB2 in
human monocytes by proteomics. Platelets proportionally
restore impaired cytokine production in human monocytes
lacking MAPK p38α, NF-κB p65, and NF-κB2. We uncovered a
vesicle-mediated platelet-monocyte-propagation of
inflammatory transcription regulators, positioning platelets
as central checkpoints in monocyte inflammation.},
keywords = {Humans / Monocytes: metabolism / Monocytes: immunology /
Blood Platelets: metabolism / Blood Platelets: immunology /
Cytokines: metabolism / Transcription Factors: metabolism /
Transcription Factors: genetics / Inflammation: metabolism /
Hyperinflammation (Other) / Immune Thrombocytopenia (Other)
/ Immunoparalysis (Other) / Inflammasomes (Other) /
Toll-like Receptors (Other) / Cytokines (NLM Chemicals) /
Transcription Factors (NLM Chemicals)},
ddc = {610},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
doi = {10.1038/s44321-024-00093-3},
url = {https://pub.dzne.de/record/284080},
}